Life from a Wellcome Trust perspective

The publication of positive results from the Ebola VSV-ZEBOV vaccine trial is being met with understandable excitement, but there is still important work that needs to be done. Charlie Weller oversees the Wellcome Trust’s Ebola funding and explains why the news is such a big achievement…

Today’s publication of research showing the efficacy of the Ebola VSV-ZEBOV vaccine represents an incredible and humbling achievement that has only been possible due to the global collaboration of researchers, NGOs, governments, industry and funders – all working towards a unified goal.

The results of this interim report include data from approximately 7,500 people given the vaccine and suggest that a single injection of VSV-ZEBOV might be highly effective in preventing people from contracting Ebola. An effective vaccine against Ebola could reduce deaths and end this devastating epidemic that has had a huge social and economic impact.

Think back to summer last year. The Ebola epidemic was in the news daily, spreading to new countries, and the number of people dying due to the outbreak was rapidly increasing.

It was a very serious situation, with no vaccines known to protect against Ebola, or drugs to treat those people who were infected.

Developing vaccines from scratch takes years. Promising Ebola vaccine candidates existed, but only one had been tested in humans and was subsequently abandoned. There were no Ebola vaccines ready to be tested in West Africa to see if they could protect people from contracting the virus.

It normally takes over two years to determine whether a vaccine is safe for use in humans and whether it can offer protection against a disease. The growing scale of the outbreak meant this process needed to be accelerated if there were to be any hope of developing a vaccine in time to impact the current epidemic.

The global community faced an enormous challenge – and time was not on our side.

In response to this the Wellcome Trust created an Ebola research fund and invited applications from researchers doing clinical trials to test vaccines and drugs that could impact the current epidemic. The first applications arrived within days of our funding announcement in August 2014.

Usually the funding cycle from application to award takes around eight months, but thanks to the good nature and hard work of many people – including reviewers, applicants and Wellcome Trust staff – who took on Ebola work on top of their usual duties, we were able to speed up the process considerably.

One of the applications we received was a proposal to assess the safety of the Ebola vaccine VSV-ZEBOV, developed originally by the Health Agency of Canada. This was one of the projects that received fast-tracked funding through the Ebola research call.

By the start of October it was funded and by the end of the month the first healthy volunteers were being vaccinated to assess safety of the vaccine. The trial sites were in Europe (Germany and Switzerland) and Africa (Gabon and Kenya). In parallel we co-funded (with the MRC and Department

As the epidemic progressed, and following positive results of the safety trial, a second proposal was received in December to assess whether the VSV-ZEBOV could protect people from Ebola. The researchers planned to use an innovative trial design where the family, friends and contacts in a ‘ring’ around a patient who had contracted Ebola would be given the vaccine.

Funding was agreed and, in March 2015, the first Ebola-infected individuals were identified and the ring vaccination began in Guinea, which continues to have the majority of Ebola positive cases.

Vaccination was given immediately or delayed by three weeks to assess the ability of the VSV-EBOV vaccine to protect against the disease. The results showed it to be so effective that as of 26th July, all trial participants are being given the vaccine immediately. The trial partners, including the Guinean authorities, WHO, Médecins Sans Frontières (MSF) and the Norwegian Institute of Public Health are now working to minimise the time taken to gather essential data that could lead to the vaccine being licensed.

The results published today are positive for two reasons. Not only does this vaccine candidate appear to give effective protection against the Zaire strain of Ebola, but we’ve got to this point in approximately eight months, rather than years.

We’re not out of the woods yet though. It’s critical that people in the affected countries continue to be given the vaccine as part of a clinical trial, to allow the research team to gather enough evidence to get the vaccine licensed.

While the community undoubtedly deserves credit for enabling this work to be fast-tracked, we should also stop to think what could have been achieved if the VSV-ZEBOV vaccine had been assessed for safety straight after the initial preclinical work.

If the safety testing work had been done earlier – before the urgency of the outbreak – the vaccine’s efficacy could have been assessed much sooner, perhaps changing the course of the epidemic and ultimately saving lives.

This transition from preclinical to safety clinical trials is a sticking point in the vaccine development pathway that is not unique to Ebola vaccines, but for many other infectious diseases. The global community has not previously been willing or able to invest in the complex and costly development process required to develop new vaccines.

If we want to reduce the risk of being caught out by future epidemics, we need to address this problem. Writing in the New England Journal of Medicine recently, Trust director Jeremy Farrar outlined a proposal to establish a global development fund to accelerate discovery and development of new vaccines.

Commenting on today’s news Farrar said, “Our hope is that this vaccine will now help bring this epidemic to an end and be available for the inevitable future Ebola epidemics. This partnership also shows that such critical work is possible in the midst of a terrible epidemic. It should change how the world responds to emerging infectious disease threats. We, and all our partners, remain fully committed to giving the world a safe and effective vaccine.”

The community has already shown the power of working together during a crisis, continuing to do so could be key to improving our future epidemic preparedness.

Like this:

Our image of the week shows coronal slices of a donated human brain during dissection at the Multiple Sclerosis and Parkinson’s Tissue Bank at Imperial College, London. Vanessa Shepherd, a final year clinical photography student at the University of Westminster, took this photograph during a work placement with our colleagues in Wellcome Images. Here she talks about her visit and the important work conducted at the Tissue Bank…

Multiple Sclerosis (MS) is a condition of the central nervous system that affects around 100,000 people in the UK. Parkinson’s, a progressive neurological disorder affects on around 127, 000 people in the UK. Most people diagnosed with Parkinson’s are over 50, but it can affect people who are much younger – as in the case of actor Michael J Fox.

During our visit to the Multiple Sclerosis and Parkinson’s Tissue Bank I was reassured by the openness and transparent approach of the labs and researchers. The clean, sterile environment was sympathetic towards the good nature of the people who had donated their tissue, and staff members were appreciative of the donations.

The researchers are striving to learn more about the brain and make further progress in fighting these Multiple Sclerosis and Parkinson’s by studying donated brain and spinal cord tissue.

The dissection I witnessed was carefully performed by an experienced neuropathologist who was happy to talk through the process and discussed what researchers are typically searching for in the identification of disease.

After the initial dissection, we watched as scientists performed a process of embedding the tissue in wax. This allows for further sectioning so that samples can be mounted on slides, ready for close assessment under a microscope.

I was surprised to learn that the researchers here welcome anyone that is considering donation – with either of these conditions or healthy brains – to get in touch with any questions they may have, and even to arrange to visit the facility for themselves.

Wellcome Images is one of the world’s richest and most unusual collections, with themes ranging from medical and social history to contemporary healthcare and biomedical science. Over 100,000 high resolution images from our historical collections are now free to use under the Creative Commons-Attribution only (CC-BY) licence.

The rise of antimicrobial resistance is one of the biggest challenges of modern times, yet there are still large gaps in public understanding of the issue. To help us focus our approach to communicating the subject, we commissioned a study to find out people’s attitudes to antibiotics and their understanding of resistance. Kate Arkless Gray discusses the results…

Headlines stating that antibiotic resistance could cost the economy trillions of dollars, or lead to millions of extra deaths a year, may influence governments and policy makers, but are they helping the public get the message about the scale of the problem we face?

Not according to research that looks at how the public engage with the issue of antimicrobial resistance.

The Wellcome Trust commissioned Good Business Ltd to conduct a number of focus groups and pair interviews with members of the public, and conversations with GPs, to explore their relationship with antibiotics. The results have highlighted a need to rethink the way we communicate the issue to the public.

While scientists and policy makers are happy using terms such as “antimicrobial resistance”, “AMR” and “antibiotic resistance”, we perhaps take it for granted that everyone understands what these means as well as we do.

Study participant’s comment

Perhaps unsurprisingly, no-one in the focus groups was familiar with the initialisation “AMR”, which often gets used as shorthand. More importantly, “antimicrobial resistance” also drew blank faces from the participants, who came from a range of social, educational and age groups. “I need a dictionary for that” commented one participant.

Even “antibiotic resistance” left the vast majority of participants confused, with many believing it is patients who build up a resistance to antibiotics prescribed, rather than the bacteria they treat.

Does it really matter?

Why should we care if people don’t accurately understand these terms? The reason is that a large part of the problem – other than the lack of new drugs being developed – is linked to people’s behaviour. It’s vital that antibiotics aren’t over-used, and when they are used it’s important that people finish the treatment course.

The research highlighted that many people feel validated when they are prescribed antibiotics, commenting, “It confirms I’m ill” and “I don’t feel like I’ve wasted the doctor’s time”. Others think of antibiotics as “a magic pill” to help them get better, without understanding that they are only effective against bacterial infections.

GP’s comment

The result of these beliefs and attitudes is that many patients put pressure on GPs to prescribe antibiotics, even when they are not needed. This was reflected in the GP interviews that were conducted, with some admitting that it can be “hard to say no” when patients are set on getting antibiotics.

What can be done?

By understanding people’s attitudes to antibiotics, and what has led them to these beliefs, we are in a better position to address misunderstandings and tackle the issues they lead to.

For example, if people think that they will develop a resistance to antibiotics, they may be less likely to finish the full course, when in fact not finishing the course could increase the rate at which resistance develops.

This study indicated that understanding that it is the microbes that develop resistance (not humans) did have an impact, but as individuals many still felt powerless to change things.

Participant’s comment

One of the most interesting outcomes was that using big numbers to show the size of the problem didn’t engage people with the issue – “You still don’t think it’ll happen to you,” said one. “The numbers are so big it just seems ridiculous,” commented another.

People were much more likely to take notice when they felt the issue might affect them, their family or friends, directly.

Know your audience

It’s important that we know our audiences and tailor communication styles to suit different people in order to best engage with them.

The language we use at work, in labs, and at academic conferences is quite different to that we use with our friends on a night out. It makes sense that what works best when communicating with health experts, economists, and politicians may well be different to what works with the general public.If we want people to fully engage with important scientific issues, such as drug resistant infections, we need to ensure that they understand them enough to be able to – and that requires us to explain things better.

Participant’s comment

We will be using the insights from this work to inform the way that we communicate and engage with the public – moving away from terms such as “antimicrobial resistance” towards “drug resistant infections” – to help clarify that it is bugs, not people, that develop resistance to drugs.

Too big to ignore

Drug resistance is too big an issue to ignore. There are several approaches to tackling it – from developing new drugs to cracking down on counterfeits – but it is important that individuals understand that they have a part to play too. Tackling misunderstandings and empowering people to make informed choices about their use of antibiotics is an essential piece of the puzzle.

Cultural change can be a slow process, but ensuring people clearly understand the problem we face is a good place to start. We hope these insights into people’s attitudes to drug resistance will enable us – and the wider community – to communicate more effectively.

The Edinburgh Festival Fringe is a hotbed of creative, artistic activity, and the Trust regularly supports productions and people who perform there. This year we have commissioned a new project – ‘TheSick of the Fringe’ – that aims bring together the people creating work about health and science at the Fringe in new and interesting ways. The project is masterminded by Wellcome Trust public engagement fellow Brian Lobel, who explains why the Fringe is the perfect place to be experimental…

The idea of The Sick of the Fringe (TSOTF) has been bubbling in my mind for a long time. Having received support and funding from the Wellcome Trust for many years – and now as an Engagement Fellow – I am fascinated by the different, but equally creative, worlds of science and performance.

TSOTF, then, is a mini-festival throughout the Fringe that celebrates and connects those worlds in a series of events, featuring artists who are already making work that uses health, illness and science as inspiration.

Talking in Open Meetings about their creative processes, these artists include: Bryony Kimmings & Tim Grayburn, whose show is about their experience as a couple dealing with mental illness; Brigitte Aphrodite who is making a musical about depression; and Simon McBurney of Complicite who is exploring the limits of consciousness and sound. We will also be running Wellcome Trust Surgeries, where Fringe participants can come and find out more about the Trust, its funding and other opportunities.

TSOTF will culminate in two main events led by neuroscientist Sir Colin Blakemore and actor, comedian, and disability rights activist Liz Carr. Their talks will address a health-related issue or topic that is close to their hearts, and will feature an ‘Opening Act’ from the Fringe, performing an extract of their work. These ‘Opening Acts’ will be selected by our network of on-the-ground curators and experts who are spending the first two weeks of the festival seeing as many related productions as possible.

This offers Fringe performers the chance to have their work seen by amazing artists (including Sheila Ghelani, Catherine Long, Katy Baird) and science communicators like Erinma Ochu, or well-established theatre critics like Lyn Gardner and Kate Copstick, not to mention many members of Wellcome Trust staff. This mix of curators and experts from a range of backgrounds ensures that the format is not a competition, but rather a curated series that invites public participation. It is an opportunity to link many interesting and varied ideas from performance and science, and to help build up a connected community in the process.

With mental health being highlighted as one of the key themes for this year’s Fringe, it seems that now is the right time to be emphasising the brilliant theatre that people are making about these topics. One of the great things about the Fringe though, is that often the most exciting work is hidden from view, percolating and fermenting in scrappy, ad-hoc environments that feel a million miles away from the Trust building on Euston Road.

Spaces like these are what many artists are used to – and what the Edinburgh Festival Fringe is all about. The Fringe celebrates the DIY and the unofficial, and results in a melting pot of ideas and creative practices all in one place.

Wellcome’s reputation and keen scientific vision has the potential to bring something really exciting to the Fringe environment and provide a new context for all kinds of creativity to merge and mingle. I hope that TSOTF will facilitate and enable people to make unexpected connections. Those DIY spaces – the areas above pubs and under staircases where ideas lurk – are not wildly different from tiny, accidental labs and back rooms where some of the earliest scientific experiments and breakthroughs took place.

Like scientific discoveries, the ideas that are seeded there need to be given the right attention to grow and develop. So while there are already artists making incredible work that takes on themes like the body, medicine, disability and research, TSOTF is about bringing them together and getting them talking. Once that happens, the possibilities for collaboration and new perspectives are endless.

Brian is looking to hear from any artists taking shows to the Fringe that would like to be part of The Sick of the Fringe. For more information, visit the project website. You can book tickets for all the TSOTF events here. Follow @TSOTFringe on Twitter and use the hashtag #TSOTF15 to connect with others. The Sick of the Fringe has been commissioned by our Engaging Science team.

The underlying genetics of Inflammatory Bowel Disease (IBD) are consistent around the world, and across diverse populations, according to a new study from the Wellcome Trust Sanger Institute.

The research, published in the journal Nature Genetics, identified 38 new regions of the genome that are associated with increased risk of IBD.

Scientists analysed10,000 DNA samples from people of East Asian, Indian and Iranian descent, as well as an existing set of 84,640 samples from Europe, in the first genetic study of IBD to include individuals from diverse populations.

Researchers had previously identified 163 variants in the genome that conferred a greater risk of IBD, however this large-scale research had only ever been conducted in Europe. The inclusion of the non-European samples, allowed a further 38 regions to be identified, though this is thought to be due to the increased sample size, rather than regional differences.

Despite the similarities, researchers did identify variants in a gene called NOD2 which increases risk of the disease in Europeans but these variants are not present in Asian populations. At other genetic locations, the variants are present in both European and East Asian samples but seem to have a much stronger effect on disease risk in Asian populations.

“The prevalence of IBD has increased dramatically in Asia over the last 50 years, probably due to lifestyle changes brought about by economic growth” says Dr Carl Anderson, a corresponding author from the Wellcome Trust Sanger Institute.

“We are now able to compare genetic risk profiles of IBD across diverse populations to find out how similar they are. Discovering differences can provide us with biological insights that would be missed if we were to focus our efforts on just a single population. In turn, this can lead to the identification of new drug targets.”

Repairing liver damage with stem cells

The livers of mice with severe liver failure have been repaired using stem cells in a major new study published in Nature Cell Biology.

The study is the first of its kind to restore function to a severely damaged liver in live animals using stem cells. It is hoped that if the technique can be shown to be effective in humans, it could offer a potential alternative to liver transplants in future.

Although the liver is able to repair itself, diseases such as cirrhosis or acute liver failure leave it damaged beyond repair. Scientists transplanted liver stem cells into mice with liver failure and observed the effect these cells had over several months. They found that major areas of the liver had in fact regrown, increasing the overall function of the liver.

Previously, essential liver cells called hepatocytes had been used for transplantations, but their lack of ability to grow in laboratory conditions limits their use. Liver stem cells are able to grow well in lab conditions and also have the advantage of being able to change into all types of cells required in the liver.

Professor Stuart Forbes, of the MRC Centre for Regenerative Medicine at the University of Edinburgh, said: “Revealing the therapeutic potential of these liver stem cells brings us a step closer to developing stem cell based treatments for patients with liver disease. It will be some time before we can turn this into reality as we will first need to test our approach using human cells. This is much needed as liver disease is a very common cause of death and disability for patients in the UK and the rest of the world’’

New target in the fight against malaria

A drug that targets a malaria patient’s own proteins rather than the parasite itself may offer a new hope for treatment of the disease.

The new research from the Wellcome Trust Sanger Institute shows how the drug is able to target a human protein relied upon by the malaria parasite to invade our red blood cells. This is especially important given that the rapidly-evolving malaria parasite, Plasmodium falciparum, has rendered front-line antimalarial drug, artemisinin, largely ineffective.

Scientists investigated the PfRH5 protein of the P. falciparum parasite, which must bind to the protein basigin, on the outer surface of our red blood cells in order to invade and infect them. By introducing an antibody that was targeted to the basigin protein, the malaria parasite was effectively blocked from binding to, and invading, red blood cells.

The antibody was also able to efficiently clear already-established malarial disease in mice, with the levels of infection falling to undetectable levels within 72 hours of treatment.

“This counter-intuitive approach to malaria treatment leaves the parasite powerless,” explains Dr Zenon Zenonos, a first author from the Wellcome Trust Sanger Institute. “If the parasite can’t bind to the surface of our red blood cells and invade, it can’t reach the next stage in its lifecycle, so it dies. There’s nothing the parasite can do to get round it, as the interaction is absolutely essential for infection to occur.”

Congratulations to Professor Emilie Savage-Smith and Professor Simon Swain who have been elected Fellows of the British Academy for the humanities and social sciences. The researchers, from the University of Oxford and the University of Warwick respectively, hold a joint Wellcome Trust Senior Investigator Award for a project titled “A Literary History of Medicine: The Best Accounts of the Classes of Physicians by Ibn Abi Usaybi`ah (d. 1270)”.

Like this:

Earlier this month, Medicines for Malaria Venture (MMV) won the Open Data Innovation Award, one of five open data awards presented by Tim Berners-Lee’s Open Data Institute. Their ‘Malaria Box’ contains 400 compounds and is available – free – to researchers looking to develop new malaria medicines. In return for the Malaria Box, results from research must be published in the public domain to help others in the field. We asked Timothy Wells, MMV’s Chief Scientific Officer, to tell us more…

At MMV we live at the interface between academia and industry – we’re a Swiss charity, but full of people with industrial experience. We have a goal of catalysing the discovery, development and delivery of new medicines against malaria.

We asked ourselves ‘how can we help to build a world where people share their ideas to help develop medicines against diseases of poverty?” These diseases kill children throughout the world.

Seven years ago, we realised it was possible to test compounds for their activities directly against the malaria parasite, and that advances in miniaturisation meant we could test a compound for as little as $1. That’s a hundred times cheaper than it was a decade ago.

We approached pharmaceutical companies and offered to organise getting their compounds tested – both inside the companies, and with our academic partners. Six million compounds and some 20 companies later, we found we had 30,000 new hits, or starting points, for malaria projects.

Many of partners allowed us to publish these structures, but we found this was not what people really wanted. Most researchers are biologists and clinicians and they wanted real compounds to test. That’s when we designed our ‘Malaria Box’, pictured pictured above. The Malaria Box contains a distillation of some of the 30,000 ‘hits’, and anyone who wants it can have it to test against their parasite or pathogen.

So far over 200 labs have asked for the Malaria Box, including groups in Africa, South-East Asia and South America. Already several new interesting leads have been identified in other parasites, infectious diseases, and even one idea in cancer. We ask that the research is published in the public domain and we hope that this openness about the ideas and results will lead to new discoveries that will benefit the children of the world.

The Wellcome Trust supports MMV and you can find out more about their Malaria Box on the MMV website.

Like this:

At the Wellcome Trust, peer review plays a fundamental role in our decision-making process, and we rely upon high quality expert advice from reviewers to enable us to select the best researchers and proposals to fund. Alyson Fox, Head of Grants Management, describes two recent developments to our peer review process.

Like any funding body, we receive far more grant applications than we are able to fund, and deciding which projects receive our support is not easy. Peer review continues to form an essential part of our decision making when awarding grants, either through written referee reports or in the form of our funding committees. We currently have over 300 committee members, serving on Expert Review Groups, Interview Committees, Selection Panels or scheme-specific committees.

These members come from a wide range of organisations – universities, research institutes, pharmaceutical and biotech companies, and policy organisations, both within the UK and internationally – but are all chosen because they are experts in their field and we believe offer the most appropriate insight and advice.

There is an ongoing turnover of these committees and new members are usually identified through various searches or recommendations, but this week we will be inviting applications for new committee members. In doing so we aim to improve the diversity of membership, and we will create a pool of prospective members across our Science, Innovations, and Humanities and Social Science portfolios which we will draw upon when creating new committees, refreshing membership of existing committees or co-opting experts to specific meetings.

Credit: Wellcome Library

Our committees are at the heart of what we do, so we have high expectations of members. Successful applicants need to have an excellent track record in research for their career stage, consistent success in securing competitive funding, experience in the assessment of research proposals or publications, and, importantly, the ability to consider and critique research outside their immediate area.

The funding committees are helped in their decision-making by written peer reviews – last year alone we received over 5000 written reviews. While peer review may be regarded as ‘part of the job’ for researchers, we recognise the effort and commitment that referees show and believe that this should be acknowledged. For that reason we are publishing the names of those who have contributed peer reviews for the Trust, and are writing to institutions informing them of who as acted as a reviewer for our grant applications.

The members of our committees and those who provide written peer review can be found on our website. We’d like to take this opportunity to once again extend our thanks to our all existing reviewers and committee members, and we look forward to receiving applications for these new positions.

If you are interested in becoming a funding committee member, further information and application details can be found here. The closing date for applications is 9th September 2015.

Like this:

Public attitudes to science have evolved over time, but getting a reliable impression of how people view the big issues is no easy task. The Wellcome Trust Monitor is a unique, large-scale survey that is conducted every three years to look at changing attitudes to science. Our third Monitor survey is currently in progress, and Wellcome Trust project manager Ethan Greenwood explains what we hope to learn…

At the Wellcome Trust we are champions of public engagement with science, but what about scientists’ engagement with the public? Sometimes it is important for us to step back and look at things through a different lens, and the Wellcome Trust Monitor aims to shine a light on people’s attitudes to science.

The Trust introduced the Monitor survey in 2009 to help inform our work in areas where the public perspective is critical. Results from the 2012 Monitor revealed that although terms like “human genome” have become an everyday part of our vocabulary, public understanding of these terms was relatively low. Insights like this can be used to help advise scientists how best to communicate their work more effectively, and also feed into our public engagement work. This is just one example of why it is important to step outside of the scientific community and talk to others.

These days surveys are ten-a-penny, but ensuring the results are from a representative sample of the UK public, and not skewed by bad question design or small numbers of responses, is a different matter. Aside from the Public Attitudes to Science Survey (PAS) commissioned by the government (last conducted in 2013), the Wellcome Trust Monitor is the only survey that offer reliable insights into current public thinking about science.

When conducting the Monitor survey, Ipsos Mori uses random sampling to reduce the problem of selection bias, with only those selected able to answer the questions. Had the survey been conducted online or by post, there is a risk that only those people interested in science would respond, thus failing to represent the population as a whole. For example the last Monitor in 2012 was the first representative survey to look at awareness and usage of cognitive enhancement medication, which established a benchmark for usage in the UK, even though there were previous non-representative online readership surveys. (This previous post by Patrick Sturgis goes into more details about how we ensure that the Monitor is scientifically robust.)

By repeating questions from previous Monitor surveys we can begin to build up a picture of changing attitudes and trends over the years. These results help us to get an overview of the position of science in society.

We have also added new questions to probe important areas of interest. For example, there have already been surveys on use of antibiotics, but the current Monitor survey will look at attitudes to them, and whether understanding the issue of drug resistant infections is associated with more responsible use of antibiotics. We can also use results from the Monitor survey to inform our upcoming education and public engagement initiative – “The Crunch”, which will examine the relationship between our food, our health and our planet.

Science touches every part of our lives in some way, and if we want to include people in the important conversations about it, we must first understand their existing perceptions and concerns. The Wellcome Trust Monitor is an essential tool for enabling us to gain these insights.

The third wave of the Wellcome Trust Monitor is currently being conducted and we make the full dataset and findings publicly available in 2016. Previous results can be found on the Wellcome Trust Monitor section of our website.

Professor Abdisalan Noor is a Wellcome Trust Research Fellow at the Kenya Medical Research Institute/Wellcome Trust Research Programme (KEMRI-WTRP) in Nairobi, Kenya. He is also a Visiting Professor at the University of Oxford, in the Centre for Tropical Medicine and Global Health. He works on a wide range of projects covering malaria, mapping and malnutrition, and we asked him to tell us more…

What are you working on?

I am funded by the Wellcome Trust to work on methods for mapping Plasmodium falciparum malaria risk in low-transmission countries in Africa. I am also a co-applicant on a Wellcome Trust Sustaining Health grant to investigate the social, spatial and environmental determinants of malnutrition in Kenya.

My other research is based on developing epidemiological profiles of malaria for high burden countries, in order to support rational planning of malaria control. This is a project supported by the UK Government under the Information for Malaria (INFORM) project, but it is built on science funded by the Trust.

What does your average day involve?

I always keep a list of things to do. I start the morning by responding quickly to important emails and then as part of my role as the Director of the Nairobi Programme, have a quick meeting with the Head of Operations.

I then attend to any issues within the Programme and follow this with updates from members of the Spatial Health Metrics group that I lead. After that I focus on the rest of my day’s work, which involves assembly and analysis of data, drafting of manuscripts, reading theses from my students, reviewing papers I have been assigned from journals and documents from technical committees that I sit on. I also try and find time to read important publications in my field and often travel to my study countries. This requires some substantial preparatory work.

Malaria prevalence in Africa, 2000-2010

Why is your work important?

Malaria is a major contributor to the burden of disease in Africa. My work on mapping malaria transmission intensity, assessing the impact of malaria control in Africa, and helping countries use sound epidemiological evidence for control, all contributes to better ways of controlling malaria.

What do you hope the impact of your work will be?

I hope the work will provide useful insights into the malaria epidemiological transition in Africa, and contribute to sound malaria control policies. I have an emerging interest in general health vulnerabilities of African households, the role malaria plays and their resilience and adaptive mechanisms.

How did you come to be working on this topic/in this field?

It was down to an unexpected twist in my life. I trained in surveying and geographic information systems in an Engineering Faculty but never really wanted to pursue a traditional career in surveying or related work.

I was interested in research and got a position as an unpaid mapping intern at the International Livestock Research Institute in Nairobi. A few months into my internship an advert came out in the newspaper for a research assistant position at the Nairobi office of the KEMRI-WTRP under Professor Bob Snow. I interviewed for this post, got it, and have not looked back since.

How has Wellcome funding helped you/your research/your career?

Immensely! The Wellcome Trust funded my PhD studies and has since been a primary funder of my work. The Trust has been supportive of my work and more broadly that of the Kenya Major Overseas Programme.

Which question about your work do you most dread – and why?

“How many people die of malaria in Africa?” There is no precise data to answer this question.

Tell us something about you that might surprise us…

I don’t like heights – but I do like classic cars!

What keeps you awake at night?

Work and the welfare of my family and staff.

What’s the best piece of advice you’ve been given?

The best piece of advice I have been given is ‘Always start with asking the right question’.

The chain-reaction question, set by our previous spot-lit researcher, Dr Lolitika Mandal, is this: What will you do if one of your ongoing projects gets scooped? (i.e. Someone else publishes results on something you’re working on before you publish yours?)

Interesting question. This is not uncommon especially where more than one group is working on the same question. Multiple groups involved in working on the same research area is not always such a bad thing as it allows for different but complementary approaches.

If someone scoops one of my ongoing projects it is natural that my initial reaction would be one of disappointment, which may take a few good days!! However, I would move on to asking whether my ‘competitors’ have done a good job of answering the fundamental questions and whether there are remaining important unresolved issues. Very often there are.

Film, theatre, literature and art regularly explore challenging subjects but the same cannot usually be said for video games. This week’s image is from a game currently in development, Hellblade, which hopes to provide a new perspective on the complex and challenging subject of mental health conditions.

This image – a still from the game – focusses on its protagonist, Senua. She is a Celtic Warrior who experiences psychosis in the form of hallucinations and delusions as she journeys on a quest of redemption. Players must put themselves in her shoes while she attempts to survive and thrive in a new and mysterious world, whilst being uncertain about what is actually real. By playing the game as Senua they will more actively participate in this process of exploration and discovery, rather than being a passive observer of someone else’s issues.

The developers, Ninja Theory, have been working in collaboration with Paul Fletcher, Professor of Health Neuroscience at the University of Cambridge, to ensure that Senua’s experiences are portrayed truthfully and with sensitivity. Involving Paul at this very early stage has not only helped the team to understand mental health in greater depth, but his input has also been felt in the creative process, marrying up elements of the science with a compelling narrative and beautiful art.

The next stage for Hellblade will involve deeper engagement with patient groups and organisations, as well as continuing the collaboration with Paul. The game is supported by funding from our Broadcast, Games and Film team and is due for release in 2016. You can watch the trailer and follow the development through a series of video diaries on the Hellblade website.

Like this:

Today the Wellcome Trust announced a £6.4M Strategic Award to researchers at the University of Oxford, UCL, the MRC Cognition and Brain Sciences Unit and the University of Exeter to investigate whether mindfulness training could help teenagers improve their mental resilience. Raliza Stoyanova, Wellcome Trust Senior Portfolio Developer in the Science Division, explains why, when more and more people are turning to techniques such as mindfulness, a study like this is important…

Half of mental health disorders have their onset before age 15, and there is growing evidence that the teenage brain undergoes significant change. This time of heightened brain plasticity offers a valuable opportunity to try and foster resilience and potentially prevent the onset of mental illness.

There is promising evidence from a number of small studies that mindfulness-based techniques are well accepted by teenagers and may be beneficial in enhancing well-being and reducing stress and depressive symptoms. However, to be sure of the efficacy of mindfulness training, a definitive, randomised controlled trial is needed. Today, we are pleased to announce that we are committing £6.4 million to study the effectiveness and psychological mechanisms of mindfulness training in the largest such trial to date.

We know that there is a great public appetite for meditation techniques such as mindfulness, with apps such as HeadSpace (which has been downloaded more than 2 million times in 150 countries) and short mindfulness courses becoming increasingly popular. Methods rooted in mindfulness are said to help with a range of health problems, from insomnia and high blood pressure, through to improving responses to pain.

Students at UCL Academy in Swiss Cottage have been practising mindfulness as part of their school day.

Mindfulness encourages us to be more present in the moment and to become not only more aware, but also more accepting of our thoughts and bodily sensations. The human mind has a natural tendency to wander so mastering techniques that keep us in the here and now can take a while. However, learning to reduce the urge to immediately react to distracting or unpleasant thoughts and sensations has been linked to benefits for both mental and physical health.

As well as helping with general wellbeing, mindfulness can be beneficial to those with mental illness, or a history of mental illness. The National Institute of Clinical Excellence (NICE) recommends mindfulness-based cognitive therapy as a way to reduce future depressive episodes for individuals with recurrent depression. For those who are healthy, the technique can improve various aspects of cognition, such as ‘working memory’ (the way that we temporarily store and interrogate information) and attention.

The £6.4 million research programme, announced today, aims to answer whether mindfulness training can benefit teenagers across the full spectrum of mental health- both those who are flourishing and those who may be at some risk of developing mental illness in the future. This definitive randomised controlled trial will include more than 6000 teenagers, across 76 schools, who will receive either ten weeks of mindfulness training, or their usual personal, social, health, economic, education (PSHE) lessons. Following the period of training, students will be followed up for two years, with researchers analysing the relative effects on risk of depression, wellbeing, and anxiety, as well as peer-relationships and school performance.

Alongside the trial in schools, in a set of laboratory studies, researchers plan to examine what components of cognitive and social processing mindfulness enhances, as well as whether the training is more effective at some stages of adolescence than others.

Throughout the study, the researchers will take advice from parents, teachers and students to ensure that the programme fits within the context of UK schools, and that if shown to be of benefit it could more easily be rolled out in the future. The research will compare different ways of training large numbers of teachers to deliver the mindfulness course (e.g. through a guided online course versus face-to-face lessons) and will also examine whether teachers themselves report any benefits from learning and practicing the technique.

Mental illness takes a huge personal toll on the patients and families it affects, and has a vast economic cost. According to recent estimates, the cost of depression alone is £11 billion a year in the UK. Relative to this burden, mental health research receives a disproportionately low amount of research and charity funding, and within that, the majority has focused on treatment. Clearly, developing new drugs and psychological therapies and methods to deliver them at scale is important and the Wellcome Trust plays an important role in supporting such research. However, it is also crucial to fund research into prevention.

By supporting this research programme we hope that we will gather more conclusive evidence about whether mindfulness is an effective way of improving mental resilience in teenagers or not and how best and most cost-effectively it might be implemented. Although an intervention such as mindfulness may have a modest effect at the individual level its potential to shift a whole population towards greater resilience and wellbeing holds great promise.

For more information about the new study assessing the effectiveness of mindfulness in schools please visit the Wellcome Trust website.

Like this:

As many people are aware, clinical research is an area of Wellcome Trust activity which is particularly close to my heart. In my own career I have had first-hand experience of juggling a job as a hospital doctor with a clinical research interest, and specialist training. Some might say I made life even harder for myself by changing specialism from neurology to infectious diseases in my early thirties. Since then, the majority of my career has been spent in Vietnam, where until very recently I was still doing twice-daily ward rounds, while also conducting and publishing research on avian flu, dengue fever, typhoid, TB and a range of other infectious diseases.

My impression on returning to the UK a year and a half ago is that the challenges facing a clinician wanting to pursue research are still there – particularly in establishing yourself early in your career. However, the UK is a unique place to be a clinical researcher, and there are really exciting opportunities thanks to what we, the NIHR, MRC, CRUK and other charities offer, and also because the NHS provides healthcare for the vast majority of people in the country. Clinician scientists are a hugely valuable asset to the NHS and, more widely, they are the interface between clinical medicine, public health and basic research.

Stem cell research. Credit: Wellcome Library

The Wellcome Trust has long recognised this key role for clinically qualified researchers. One example of a clinician researcher we have supported for a long time is Sadaf Farooqi at the University of Cambridge, who has been funded by Wellcome Trust clinical schemes since the late 1990s. Her team’s research into the genetics, physiology and neuroscience of severely obese patients has directly led to improved diagnostics for a range of obesity syndromes and a mechanism-based treatment for a specific obesity disorder, congenital leptin deficiency. This transformational treatment has been used successfully around the world, improving the lives of patients with this deficiency.

At the Wellcome Trust we have been listening to the clinical research community, both through individual meetings and through workshops with the directors of the Wellcome Clinical PhD Programmes, clinical trainees, funders, medical school deans and others. What we have heard from you is that there is scope to update how we support clinical researchers, so that our funding and approach is more flexible, and better at supporting diversity among clinical trainees.

We also want to make sure that our funding is suited to the pressures facing early-career researchers who take on the challenge of gaining a clinical specialism, whilst also conducting research, and maintaining a home life.

The first change we are introducing is to deliver all our PhD training to clinicians exclusively through tailored PhD programmes from autumn 2016 onwards, meaning the end to the Research Training Fellowship. We believe that training small groups of PhD students in programmes gives the best opportunity to embed clinical academic training within universities and university hospitals, to build a community of researchers, and enhance mentoring.

Theatre sister in surgery. Credit: Wellcome Images.

We will be launching a competition in autumn 2015 for new clinical PhD programmes, and we envisage that this expansion to our existing portfolio will ensure that clinicians from across the range of specialities, in all corners of the UK, the Republic of Ireland, and in our Major Overseas Programmes, will be supported. We encourage innovation in the creation of new PhD programmes. For example, programmes could include elements of industrial collaboration, be hosted across multiple institutions, be open to allied health professionals or those working in medical humanities.

The second change we are introducing is the establishment of a Postdoctoral Clinical Scientist Fellowship, consolidating two of our existing schemes into a single, flexible offer.

We are also providing additional funding which means that our capacity for supporting clinicians at a postdoctoral level will increase by 50%. This enhanced support at the postdoctoral level is in line with changes we have introduced for our basic science fellowships. The new approach also allows the possibility of longer term support and greater accommodation for balancing research and clinical training. It will be open to those who are re-entering academia after career breaks or extended periods of clinical training, and will adapt to the changing clinical training model.

We believe that these changes, supported by significant additional Wellcome Trust funding, will help improve diversity among the clinical trainees and clinicians we fund, and particularly help early career researchers to establish themselves in their chosen fields.

As ever, we welcome feedback on these changes.

You can email your feedback to sciencegrants@wellcome.ac.uk. More details about our new clinical career pathway, and details of how to apply will be available on the Wellcome Trust website in due course.

Like this:

European law has a significant influence on many aspects of national law in the UK and other member states, including research. One aspect that is currently of concern to the Wellcome Trust lies within new rules on medical devices, which have the potential to restrict genetic testing in the EU. Policy officer Will Greenacre explains why one size does not necessarily fit all:

The European Union is currently redrawing the rules governing the manufacture and sale of medical devices, including in vitro diagnostic devices. These devices range from blood glucose monitoring kits for diabetics and home pregnancy tests, right through to complex hospital assays. These rules, which will be directly binding in national law for all EU member states, also apply to genetic tests, and an amendment proposed by the European Parliament to the draft regulations has the potential to limit the availability of genetic tests by placing very specific requirements on their use.

New genetics tests for a variety of diseases are continuously being developed

The field of genetics has the potential to transform medicine and healthcare, both through the development of novel treatments, and enhancing our understanding of health and disease states. We are already seeing genetic testing embedded in some aspects of healthcare, with initiatives like Mainstreaming Cancer Genetics supporting easier access to genetic testing for cancer patients – making it a routine part of their treatment. Knowledge of a person’s genetic makeup – and that of their tumour – can help doctors to understand the cause of their disease and plan the most effective, ‘targeted’ treatments.

It’s not limited to cancer genetics. Genetic testing is becoming more prevalent in other areas of medicine, including for conditions like cardiovascular disease and dementia. As technology advances, it has the potential to benefit many areas of healthcare by providing greater insights into our genetic susceptibility to disease, and how our genes can inform the best approaches to treatment.

The new regulations currently being discussed in the European Union could hinder these developments. The suggested amendment proposes that genetic tests can only be conducted by a qualified medical professional, and only after mandatory genetic counselling has been given and full consent provided. While this is appropriate for some types of tests, where the results could have profound implications for the patient and their family, to apply it to genetic tests where consent may be implicit would risk restricting the availability of tests for other conditions.

This raises concerns due to the wide scope of genetic testing, with new tests and diagnostics being developed all the time. As testing becomes a more common and integrated part of healthcare it might be that in hospitals, for example, tests would be carried out by nurses or laboratory staff without the patient present. To require genetic counselling before and after tests in all circumstances would be unworkable. While we support the role of genetic counsellors, requirements for consent and counselling have to be proportionate, taking into account the nature of the test and the implications of the information for the patient and their family.

We will be taking forward discussions with European Commission officials and key MEPs involved in the negotiations in the coming weeks and months, ahead of final negotiations between the European Parliament, the Commission and the Council of Ministers which are expected to begin in the autumn. Regulation of this area is a complex issue, but it must aim to strike the right balance between protecting patients and encouraging innovation for their benefit.

Read more about the background to the in vitro diagnostics regulation and our activities – as well as other areas of EU policy that we are involved in – on the EU affairs page of the Wellcome Trust website.

Cancer surgery and biopsies may play a role in the progression of cancer according to new Wellcome Trust-funded research published in the journal EMBO.

Sometimes described as ‘the wound that doesn’t heal,’ there has been a longstanding link between tissue damage, wound healing and cancer. However until now there has been little research into the direct impacts of cancer surgery or biopsies on the progression of the disease.

Researchers investigating how inflammatory cells react to cancerous wounds used genetically engineered zebrafish larvae that sporadically produce pre-cancerous cells in their skin. They found that inflammatory cells, mainly a specialised type called neutrophils, rapidly migrated from wounds (such as those caused by surgery) to the pre-cancerous cells in the Zebrafish skin, causing rapid growth at these sites.

By then studying the inflammatory response in human melanoma samples, the researchers were able to examine how this process could play a role in human cancer progression. They found a strong link between the presence of inflammatory cells at the site of open wounds in melanomas and the division of the cancerous cells. This was subsequently associated with a poor predicted outcome.

Wellcome Trust Senior Investigator Professor Paul Martin, from Bristol University said: “All surgery and biopsy collections carry an element of risk and this study reveals a further potential risk for clinicians to consider. For the first time we can now watch the interplay between inflammatory cells visiting wounds and nearby cancer cells, and use this to determine why and how this occurs and how we might learn to prevent it.”

Exhausted immune cells

Our body’s immune cells can become ‘exhausted’ in the face of unwanted infections and can actually damage the very body they are trying to protect.

New Wellcome Trust-funded research published in Nature investigated how T cells, a specialised type of immune cells, can be ‘exhausted’ by inhibitory signals which prevent them efficiently fighting unwanted invaders. In this state, T cells are unable to clear chronic infections, such as Hepatitis C or HIV, from the immune system.

The researchers found that the pattern of genes turned on and off in patients with chronic infections is very similar to that of patients with autoimmune diseases (for example Crohn’s or Lupus) suggesting that the T cell ‘exhaustion’ is seen in both cases.

In patients with chronic infections, immune exhaustion reduces the capacity of the immune system to fight infections, meaning a poorer health outcome for the patient. However, the opposite is true for patients with an autoimmune disorder; an exhausted immune response leads to less severe disease and fewer relapses.

Dr Eoin McKinney, a Wellcome Trust-Beit Research Fellow from the Department of Medicine at the University of Cambridge explains: “We know that the way our bodies respond to infection and to autoimmune diseases differs between individuals. In part, we believe this is due to a process known as T cell exhaustion. For effective treatment, we need to exhaust our T cell responses in autoimmune diseases – and hence limit the attack on our body – and to reverse exhaustion when the fight is against unwanted invaders, such as viruses or cancer.”

A traumatic night’s sleep

A good night’s sleep has often been suggested as a cure for all manner of ailments, but a new study published in Sleep suggests that sleep deprivation might actually help reduce flashbacks in those that have experienced a traumatic event.

Wellcome Trust-funded researchers investigated the effects of sleep deprivation in a clinical setting, showing participants film scenes containing traumatic content. They were then either sent home to get a full night’s sleep, or deprived of sleep in the laboratory.

Through participants’ diary entries, scientists noted that those deprived of sleep experienced fewer intrusive memories than those who got a good night’s sleep at home. Sleep is known to improve memory performance and the research shows that depriving people of it may help to prevent people consolidating memories of a trauma, leading to fewer flashbacks.

Dr Kate Porcheret from the Wellcome Trust-funded Sleep and Circadian Neuroscience Institute said: “Finding out more how sleep and trauma interact means we can ensure people are well cared for after a traumatic event. These are really important research questions to pursue further. For example, it is still common for patients to receive sedatives after a traumatic event to help them sleep, even though we already know that for some very traumatised people this may be the wrong approach.”

Radioactivity re-purposed

A radioactive tracer originally used to detect bone cancer has been re-purposed to help identify patients at risk of heart attacks or strokes.

Atherosclerosis – commonly known as hardening of the arteries – occurs when arteries become blocked by a build-up of fatty deposits called plaques. These plaques, which contain calcium, can be unstable and detach from the artery wall and can cause fatal heart attacks or strokes if they travel the heart or brain.

Wellcome Trust-funded researchers injected patients with sodium fluoride tagged with very small amounts of radioactive tracer. The tracer’s journey around the body was tracked using a combination of scanning techniques, allowing scientists to see exactly which tissues it accumulated in.

Not all calcium-containing plaques in the artery are unstable – in some patients they are completely stable, although it is unclear why. Researchers discovered that the tracer only accumulated in unstable plaques and not any surrounding tissue, allowing these patients to undergo surgery to have them removed, reducing their risk of serious illness.

Dr James Rudd, a cardiologist and researcher at the University of Cambridge adds: “Sodium fluoride is a simple and inexpensive radiotracer that should revolutionise our ability to detect dangerous calcium in the arteries of the heart and brain. This will allow us to use current treatments more effectively, by giving them to those patients at highest risk. In addition, after further work, it may be possible to use this technique to test how well new medicines perform at preventing the development of atherosclerosis.”

New Wellcome Trust-funded research has suggested that playing visually demanding video games may help reduce intrusive memories of past traumatic events. The study, published in Physiological Science, is the first of its kind to show that a cognitive blockade can have a positive impact on the sort of visual memories associated with stress and trauma related disorders such as PTSD.

In other news

It’s been a busy time for awards and prizes recently with numerous members of the community nominated for prestigious accolades. Congratulations to the following academics:

Wellcome Trust Governor Professor Kay Davies is to receive the American Society of Human Genetics Allan Award. The prize is given in memory William Allan, one of the first American physicians to research human genetics and hereditary diseases, and recognises far-reaching contributions to human genetics.

Professor Sir Stephen O’Rahilly has become the first recipient of the EASD-Novo Nordisk Foundation Diabetes Prize that recognises outstanding research or technological contributions to the understanding of diabetes. Professor O’Rahilly, co-Director of the Wellcome Trust-MRC Institute of Metabolic Science, holds a Senior Investigator Award which focuses on the mechanisms of human resistance to insulin.

Professor Joel Tarning is awarded the Giorgio Segré Prize for his work on the pharmacokinetic properties of antimalarial drugs in vulnerable populations. Based at the Mahidol Oxford Tropical Medicine Research Unit, a collaboration between Oxford University, Mahidol University and the Wellcome Trust, his work has made a significant contribution to the understanding of the optimal doses for key antimalarial medicines in children.

Like this:

With the Wimbledon finals this weekend and the sun shining over Trust HQ, we thought it was the perfect time for some strawberries and cream – with a twist! Over 28,000Kg of strawberries and cream will be eaten at the All England Club during the 2015 tennis championships, but our image this week is focusing on just one strawberry.

We’re giving you a look at the fruit from a whole new perspective. The strawberry above has been virtually sliced, using spin-echo magnetic resonance imaging (MRI), revealing the details of the fruit without damaging it! These virtual slices are ultra-thin and so only a small selection of them is shown in this collage.

This image has been digitally coloured, with contrast corresponding to the intensity of the MRI signal, and the hue changed to match the natural colour of the fruit.

The ancient Romans believed that strawberries could help with the symptoms of melancholy, kidney stones and halitosis, but we’re happy just to enjoy them for their sweet taste and vitamin C!

Wellcome Images is one of the world’s richest and most unusual collections, with themes ranging from medical and social history to contemporary healthcare and biomedical science. Over 100,000 high resolution images from our historical collections are now free to use under the Creative Commons-Attribution only (CC-BY) licence.

E-mail Subscription

Follow us on Twitter

Google+

Wellcome Trust

The Wellcome Trust is a global charitable foundation dedicated to improving health by supporting bright minds in science, the humanities and social sciences, and public engagement. Read more.

Commenting guidelines

By commenting on this blog you agree to abide by our Community Guidelines. Although we will do our utmost to avoid it, we reserve the right to edit, move or delete any comments which do not follow the guidelines provided.